Process for the preparation of phenylacetic acid

ABSTRACT

Phenylacetic acid is obtained by oxidation of phenylacetaldehyde with air or oxygen in the presence of a transition metal derivative e.g. a derivative of Co, Mn, Cr, Cu, Fe. Oxidation may be carried out in an inert hydrocarbon, halogenated hydrocarbon, carboxylic acid or ester, nitrile, tertiary alcohol or ketone or mixtures thereof e.g. tert. butanol and acetic adid. The catalyst may contain additionally derivatives of Group 3a or 4a metals.

United States Patent Gay Nov. 11, 1975 [5 PROCESS FOR THE PREPARATION OF 3.607.7l9 9/1971 Barone 260/523 PHENYLACETIC ACID 5 I M h l G L F FOREIGN PATENTS OR APPLICATIONS 1 e 2.136.481 1/1972 Germany 260/523 A [73] Assignee: Rhone-Poulenc S.A., Paris, France [22] Filed: Sept. 5, 1973 Primary Examiner-Robert Gerstl Assistant Examiner-Richard D. Kelly [21] Appl Attorney. Agent, or FirmStevens, Davis, Miller &

Related US. Application Data sh [63] Continuation-impart of Ser. No. 164.424. Jul 20.

l97l. abandoned.

[57] ABSTRACT [30] Foreign Application Priority Data Phcnylacetic acid is obtained by oxidation of phenyl- July 21, 1970 France 70.26829 acetaldehyde with air or oxygen in the presence of a June 2. 1971 France 71.19979 transition metal derivative e.g. a derivative of Co. Mn. Cr. Cu, Fe. Oxidation may be carried out in an inert 260/523 A; 260/599 hydrocarbon, halogenated hydrocarbon. carboxylic [51] Int. Cl- C0 C l/ C07C 51/33 acid or ester. nitrile. tertiary alcohol or ketone or mix- Field 0f Search 260/523 A tures thereof e.g. tert. butanol and acetic adid. The catalyst may contain additionally derivatives of Group [56] References Cited 33 or 4a metals.

UNITED STATES PATENTS 2.964.559 12/l960 Burney ct al. 260/523 10 Clams No Drawmgs PROCESS FOR THE PREPARATION OF PHENYLACETIC ACID This is a continuation-in-part of my application Ser. No. 164424 filed July 20th 1971, now abandoned.

The present invention relates to a process for the perparation of phenylacetic acid by oxidation of phenylacetaldehyde with molecular oxygen or a gas containing molecular oxygen.

Phenylacetic acid is an important industrial product used either as such or in the form of its salts, amides or esters (potassium phenylacetate, methyl phenylacetate or phenylacetamide) as a precursor in the manufacture of penicillin. Phenylacetic acid is also used for the preparation of phenylacetone, and certain of its esters are employed in perr'umery.

The only industrial process for the preparation of phenylacetic acid involves alkaline or acid hydrolysis of phenylacetonitrile, itself obtained by reaction of hydrocyanic acid or of alkali cyanides with benzyl chloride. Despite the good yields obtained, this process is relatively complicated and it is desirable to have available a simpler process for the preparation of phenylacetic acid.

The present invention provides a process for the preparation of phenylacetic acid wherein phenylacetaldehyde is oxidised with molecular oxygen or with a gas containing moleculer oxygen, in the presence of a derivative of at least one transition metal.

The process of the invention makes it possible to obtain phenylacetic acid in excellent yields from a starting material easily obtained by oxidation of styrene with thallic ions (see U.S. Pat. Nos. 3,048,636 and 3,452,047). The term transition metals is used in this specification to describe the metals of Groups lb, 2b, 3b, 4b, 5b, 6b, 7b, and 8 of the Periodic Classification of the Elements (Handbook of Chemistry and Physics, 45th Edition page 8-2).

Preferred catalysts to be used in the process of the invention are those consisting essentially of at least one metal derivative where the metal is at least one selected from the group consisting of chromium, manganese, cobalt, iron and copper or at least two metal derivatives where at least one metal is selected from the group consisting of chromium, manganese, cobalt, iron and copper and at least one metal is selected from the group consisting of tungsten, titanium, molybdenum, thallium, palladium, nickel, cerium, uranium, lead and silver.

Derivatives of chromium, manganese, cobalt, iron and copper can be used to catalyse the reaction. The oxidation level of the metal in the metal derivative is not critical and the derivative can be formed in situ" from the free metal, under the reaction conditions. In general, however, it is preferred to employ preformed metal derivatives which can be in the form of salts of inorganic or organic acids, of chelates or of complexes derived from monodentate or polydentate ligands. The radical associated with the metal in the catalyst is not critical for the oxidation reaction; however, for practical reasons, the metal compounds which are soluble in the reaction medium are preferentially chosen.

Metal salts which can be used, include the halides, sulphates, phosphates or nitrates; salts of organic acids, such as those of aliphatic carboxylic acids containing from I to 30 carbon atoms such as formic, acetic, propionic, butyric, hexanoic, octanoic, stearic, oleic, pal- 2 mitic and naphthenic acids; arylaliphatic acids such as phenylacetic acid; cycloaliphatic (cyclohexanecarboxylic) acids; aromatic acids such as benzoic and salicylic acids; and sulphonic acids such as methanesulphonic, ethanedisulphonic and benzenesulphonic acids. It is also possible to use chelates of the transition metals with B-dicarbonyl compounds such as the B- diketones, the B-ketoesters and the B-ketoaldehydes. Suitable B-dicarbonyl compounds include, diketones such as acetylacetone, 2,4-hexanedione, 2,4-heptanedione, 3-methoxy-2,4-pentanedione, l,l ,l-trifluoro-2,4- pentanedione, benzoylacetone and dibenzoylmethane; B-ketoesters such as methyl, ethyl or propyl acetylacetates and methyl benzoylacetate and fi-ketoaldehydes such as propionylacetaldehyde, benzoylacetaldehyde and a-formylcyclohexanone.

Specific catalysts which can be used in the process of this invention, include cobalt bromide, manganese bromide, copper bromide, cobalt chloride, manganese chloride, cuprous and cupric chlorides, chromium, cobalt and manganese sulphates, cobalt, manganese and copper phosphates, cobaltous acetate, cobaltic acetate, ferrous acetate, manganese acetate, copper acetate, cobalt octanoate, manganese octanoate, copper octanoate, copper, cobalt and manganese naphthenates, cobalt, copper and manganese stearates, cobaltous acetylacetonate, cobaltic acetylacetonate, chromium-Ill acetylacetonate, manganese-[ll acetylacetonate, ferric acetylacetonate and cupric acetylacetonate.

The reaction can be carried out in the presence of a derivative of one metal or of a combination of two or more metals. Combinations of cobalt derivatives with derivatives of other transition metals, such as V, Hg, Ru, W, Ti, Mo, Pd, Ni, Mn, Fe and Ag are very particularly suitable. The transition metal derivatives can also be combined with derivatives of metals of Groups 3a and 4a and of metals of the lanthanides and actinides groups of the Periodic Classification of the elements, (Handbook of Chemistry and Physics, 45th Edition page B2) and especially with derivatives of thallium, lead, cerium and uranium.

In this last mentioned case, the radical combined with the metal can be the same or different from that combined with the transition metal.

The amount of catalyst, expressed as a percentage by weight of metal in the reaction medium, can vary within wide limits. In general, a metal content of between 0.000l and 5% is very suitable. An amount above 5% would not provide any additional advantage for the additional cost and most frequently, a metal content below 2% is used.

If a combination of metal derivatives is used, the amount of each of the metals introduced into the reaction medium may be within the limits defined above.

The reaction can be carried out in the absence or preferably in the presence of an inert solvent. Suitable solvents, include aliphatic hydrocarbons containing at least 4 carbon atoms (e.g. butane, pentane or hexane), cycloaliphatic hydrocarbons (e.g. cyclohexane) or aromatic hydrocarbons (e.g. benzene or toluene); alkyl, cycloalkyl or aryl halides such as chloroform, carbon tetrachloride, l,2-dichloroethane, chlorobenzene. or chlorotoluenes; aliphatic carboxylic acids which are liquid under the reaction conditions (preferably acetic acid, which may be anhydrous or contain a small amount of water), esters such as methyl or ethyl acetates', nitriles such as acetonitrile and propionitrile; tertiary alcohols such as t-butanol, t-amyl alcohol and trie- 3 thylcarbinol; ketones such as acetone, methyl ethyl ketone, Z-pentanone, S-pentanone, methyl isopropyl ketone and cyclohexanone.

These various solvents can be used individually or as 4 The Examples which follow illustrate the invention and show how it can be put into practice.

EXAMPLE I a mixture with one another, in proportions which vary 5 The apparatus used consists of a vertical cylindrical according to the reaction conditions (e.g. temperature, glass reactor of 30 mm internal diameter and 270 mm nature of the solvents and nature of the catalyst). Solheight, the base of which consists of a sintered glass vent mixtures which are particularly advantageous for disc; the reactor is equipped with a gas inlet through carrying out the process are those consisting of tertiary the porous bottom, a double jacket for circulating a alcohols mixed with aliphatic carboxylic acids, hydrocooling or heating medium, an outlet tap arranged at carbons, alkyl-halides, cycloalkyl-halides or arylthe bottom, a thermometer and a reflux condenser. halides or nitriles. in these solvent mixtures, the pro- Whilst a slight stream of oxygen is passed into the reportion by weight of tertiary alcohol can vary from actor, 98 cm of l00% strength acetic acid, 2 cm of to 90%. Preferably, combinations of tertiary alcohols water, 27.1 mg of cobalt acetate Co(CH -COO),. 4 and aliphatic carboxylic acids, and more particularly of H 0 and finally 12.77 g of 94% strength by weight pheacetic acid and t-butanol, are used. Such mixed solnylacetaldehyde (representing 0.1 mol) are introvents make it possible to improve the yields of phenyladuced. A stream of cold water which keeps the concetic acid whilst restricting the formation of by-protents of the reactor at C is simultaneously passed ducts such as benzoic acid, benzaldehyde and benzyl through the double jacket. formate. 20 The oxygen flow rate is thereafter adjusted to 5 Though the oxidation process can be carried out in a llhour under normal pressure and temperature conditemperature range extending from 0 to 120C, it has tions. The disappearance of the phenylacetaldehyde is been found that the best results are obtained at temperfollowed by gas-liquid chromatography. After 8 hours atures of the order of l0 to 60C. in general, the temminutes reaction under these conditions, the pheperature employed depends on the other reaction fac- 25 nylacetaldehyde has been almost quantitatively contors such as the nature of the metal of the catalyst, and verted. the nature of the solvent. The acetic acid is removed by azeotropic distillation The oxidising agent can be oxygen or air, optionally of its binary mixture with ethylbenzene under reduced enriched in oxygen. The reaction can be carried out at pressure, at 20-25C. The distillation residue (15 g) is normal pressure by simply passing the oxidising gas into dissolved in 40 cm of benzene and the following com the phenylacetaldehyde solution. The process can also ponents are found, by gas-liquid chromatography, in be carried out under a partial pressure of oxygen which the solution obtained: has been lowered to 0.1 bar or which can be as high as 7.2 millimols of benzyl formate 50 bars. l millimol of unconverted phenylacetaldehyde Depending on the reaction conditions (particularly 2 millimols of benzaldehyde the nature of the catalyst, solvent and temperature), it 82.6 millimols of phenylacetic acid can be advantageous to keep the reaction mixture, 7.2 millimols of benzoic acid after stopping the passage of the oxidising gas, ata temthe two acids being determined in the form of their perature which can be equal to, lower than or higher methyl ester after treatment with diazomethane. than that of the oxidation temperature, so as to allow The yields relative to the phenylacetaldehyde conthe intermediate compounds of the reaction to become verted are as follows: completely converted. The optimum duration of this finishing process depends on the conditions under phenyiacefic acid which it is carried out and can be determined in each bmwic acid 13% 4 5 be nzaldehyde 2% particular case by means of simple experiments. benzyl format: 73%

The process according to the invention is very particularly suitable for being carried out continuously, in the usual apparatuses for bringing gases and liquids into EXAMPLES 2 o 19 contact.

Following the procedure of Example 1, a series of processes were carried out under the conditions, and with the results, shown in the table which follows:

Duration Ex. Solvent Catalyst TC Oxidi- Time of Finish- PA( l Degree sing contact ing introof conagent with duced, version 0, in mM of PA 2 CH=COOH CH,COOCoBr, 20 oxygen 8 hrs. 99.3 99 k (98cm')! l4.9 mg 5 l/hr. 20 mins. H10 (2 cm) 3 ditto (CHgCOOhCo, 20 air 8 hrs. 100.2 69 at 25 mg 10 l/hr. 20 mins. 4 ditto ditto 30 oxygen 5 hrs. 99.5 99.5%

5 l/hr. 30 mins. 5 ditto ditto 40 ditto 5 hrs. 100.5 99 i 6 ditto (CH,C00),C0, 20 ditto a his. I00 85.6%

5 mg 15 mins. 7 Cyclo- (AA);Co 30 ditto 7 hrs. 43.9 as k hexane (l). l00 cm 25 mg a ditto Cobalt l9 ditto 7 hrs. 991 95.5%

-continued Duration Ex. Solvent Catalyst TC Oxidi- Time of Finish PM 1) Degree sing contact ing introof conagent with duced, version 0, in rnM of PA octanoate 45 mins. (2) 9 ditto (AA),Mn, 20 ditto 7 hrs. 49.8 90.5%

78 mg 45 mins. ditto (AAMCr. ditto 8 hrs. 50.1 90

26 mg 50 ll Acetonitrile. (AAl Cu. mg 29 oxygen 8 hrs. 49.6 83.5%

100 cm 5 llhr l2 ditto (AAhFe, 25 mg ditto 8 hrs. 49.9 87.5%

30 mins. 13 ditto (AAhCo. 25 mg 30 ditto 5 hrs. 98.7 99

20 mins. 14 Ethyl ace- (AAhMn, 50 mg 30 ditto 5 hrs. 94 92 tate, 100 mins. cm 15 Benzene (AA);Co, 10 mg 30 ditto 7 hrs. 50.4 100 K00 cm 16 t-Butanol (AA),Co, 30 ditto 2 hrs. 3 hrs. 118 99.4%

30.5 mg mins.

17 t-Amyl ditto 30 ditto 6 hrs. 3 hrs. 99.5 97.2%

alcohol 18 Acetone ditto 30 ditto 4 hrs. 3 hrs. 101 99.7% 19 Methyl ditto 30 ditto 4 hrs 3 hrs 99 99.1%

isopropyl ketone Yields/PA converted Ex. Solvent PAA BA 8(1 BF( 1) 2 CH,CO0H 85 5.6% 2.04% 7.4%

(98cn1)! 11,0 (2 cm) 3 ditto 71 1.45% 13 12% 4 ditto 77.1% 4.04% 10.1% 9% 5 ditto 70.3% 15.8% 4.25% 9.5% 6 ditto 85 2.38% 4.25% 7.2% 7 Cyclo- 80 6.6% 5.15% 6% hexane 100 cm" 8 ditto 85 3.08% 3.68% 56% 9 ditto 77.7% 7.8% 7.35% 10 ditto 51 2.44% 6.75% 11 Acetonitrile, 71.9% 2.42% 6.3% 10% 100 cm 12 ditto 76.3% 2.98% 5.7% 7% l3 ditto 66.3% 18.8% 4.1% 6% l4 Ethyl ace 69.8% 13.9% 14.1% I to 2% tale. 100 cm 15 Benzene 66 12.1% 5.9% 16% 100 cm 16 t-Butanol 68.1% 24.5% 1.4% 0.3% 17 t-Amyl 85.6% 7.7% 5.6% 1.2%

alcohol 18 Acetone 57.4% 20.4% 1.5% 0.3% 19 Methyl 67.5% 17.1% 2.6% 0.7%

isopropyl ketone (HAA. PA, FAA. BA. B and BF r 2, denote the net, ,3 phenylncetic acid. benzoic acid, benuldehyde and benzyl formate radical. (2)101 mg of a solution of cobalt octanoate in cycloheune. containing 6% of metal.

as the solvent.

EXAMPLES 20 To 22 The results obtained are given in the table below:

The procedure of Example 16 is followed, using acetic acid/t-butanol mixtures of varying composition views/PA com verted,

Acetic t-Butanol. Degree Duration Ex. acid. by of con- FAA BA B BF of pasby weight version sage of weight PA, 0,

20 30 70 99.2 82 15.4 1.9 0.5 2 hrs 45 mins.

21 50 98.4 86.4 8 3.6 1 3 hrs. 22 30 97.6 9.1 3.9 1.9 2 hrs 30 mins.

-continued Yields/PA converted. t

Acetic t-Butanol. Degree Duration Ex. acid. 7: by of con- PAA BA B BF of pas it by weight version sage of weight PA. O,

EXAMPLES 23 TO 34 The procedure of Example 16 is followed, combining derivatives of various metals with a cobalt derivative.

The results obtained are given in the table which follows:

pressure of oxygen of 0.1 to 50 bars which comprises including in the reaction mixture a derivative of a metal selected from the group consisting of chromium, manganese, cobalt, iron and copper, the amount of the said metal in the mixture being between 0.0001 and 5% by weight.

Metal derivatives Degree of Yields/PA converted conversion, Ex. Nature Amou- PA PAA BA B BF nt in ppmtl) of metal 23 W(CO), 100 97.7 71.5 16.1 4 0.3 24 Manganese acetylacetonate 25 96.6 73.1 17.9 6.4 0.3 25 Titanyl acetylacetonate 50 96.6 77 14.8 7.8 26 FeCl, 100 98.6 77.7 l7.9 2.4 0.3 27 Molybdenum naphthenatc 100 92.2 80.3 8.9 6.6 0.3 28 Thallium acetate 50 98.5 83.6 14 2.1 0.3 29 PdCl, 15 96 84.6 8.1 5.3 0.3 30 Nickel acetylacetonate 50 97.2 85.1 9.7 4.9 0.3 31 Ammoniacal cerric nitrate 50 97.8 85.6 10 4.2 0.3 32 Uranyl acetylacetonate 100 96.8 86.4 7.6 5.8 0.3 33 Silver nitrate 50 97 87.l 8.1 4.5 34 Lead octoate 100 95 88.8 4.9 6.1 0.3

(1) Parts by weight per million in the reaction mixture.

EXAMPLE 35 2. A process according to claim 1 wherein the metal 35 is present in ionic form as a salt or as a chelate derived This Example was carried out in apparatus similar to that described in Example 1. The apparatus was charged with phenylacetaldehyde manganese acetylacetonate lead octoate isobutylacetate 0.031 g (5 mg manganese) 0.044 g (10.5 mg lead) sufficient to produce 100 cc of mixture The reaction mixture weighed 89 g. The contents of the reactor were brought to a temperature of 30C. and then oxygen was introduced at the rate of [0 liter per hour measured at normal temperature and pressure. These reaction conditions were maintained for 7% hours. The reaction product was then analysed by gas liquid chromatography and the following products identified:

phenylacetic acid 90 millimoles benzoic acid 7 millimoles benzyldehyde 4.4 millimoles phenylacetaldehyde 1.5 millimoles benzylformate 4.2 millimoles from a dicarbonyl compound or as a complex of the metal.

3. A process according to claim 1 wherein the metal derivative is cobaltous acetate, cuprous acetate, cupric acetate, ferrous acetate, manganous acetate, chromium-lll acetate, cobaltous octanoate, manganic acetylacetonate, chromium-ll] acetylacetonate, cupric acetylacetonate or ferric acetylacetonate.

4. A process according to claim 1, wherein the said metal is cobalt and the reaction mixture also contains a derivative of W, Ti, Mo, Tl, Pd, Ni, Ag, Ce, Pb or U.

5. A process according to claim 1, wherein the said metal is cobalt and the reaction mixture also contains at least one derivative of a metal of Group 3a or 4a of the Periodic Classification of Elements or of the lanthanide or actinide Groups selected from thallium, lead, cerium and uranium.

6. A process according to claim 1 wherein the oxidation is carried out in the presence of an inert solvent.

7. A process according to claim 6 wherein the inert solvent is at least one aliphatic hydrocarbon containing at least 4 carbon atoms, cycloaliphatic hydrocarbon or aromatic or alkyl aromatic hydrocarbons, alkyl-, cycloalkyl-, or aryl halide or an aliphatic carboxylic acid or ester thereof, a nitrile, a tertiary alcohol or a ketone.

8. A process according to claim 7, wherein the solvent is acetic acid, cyclohexane, benzene, ethyl acetate, acetonitrile, tert. butanol, tert. amyl alcohol, acetone or methyl isopropyl ketone.

9. A process according to claim 7, wherein the solvent is a mixture of a tertiary alcohol with an aliphatic carboxyiic acid and to 10% by weight of a tertiary alcohol. 

1. A PROCESS FOR OXIDISING PHENYLACETALEHYDE TO PHENYLACETIC ACID WITH MOLECULAR OXYGEN OR A GAS CONTAINING MOLECULAR OXYGEN AT 0* TO 120*C, AND A PARTIAL PRESSURE OF OXYGEN OF 0.1 TO 50 BARS WHICH COMPRISES INCLUDING IN THE REACTION MIXTURE A DERIVATIVE OF A METAL SELECTED FROM THE GROUP CONSISTING OF CHROMIUM, MANGANESE, COBALT, IRON AND CIPPER, THE AMOUNT OF THE SAID METAL IN THE MIXTURE BEING BETWEEN 0.0001 AND 5% BY WEIGHT.
 2. A process according to claim 1 wherein the metal is present in ionic form as a salt or as a chelate derived from a dicarbonyl compound or as a complex of the metal.
 3. A process according to claim 1 wherein the metal derivative is cobaltous acetate, cuprous acetate, cupric acetate, ferrous acetate, manganous acetate, chromium-III acetate, cobaltous octanoate, manganic acetylacetonate, chromium-III acetylacetonate, cupric acetylacetonate or ferric acetylacetonate.
 4. A process according to claim 1, wherein the said metal is cobalt and the reaction mixture also contains a derivative of W, Ti, Mo, Tl, Pd, Ni, Ag, Ce, Pb or U.
 5. A process according to claim 1, wherein the said metal is cobalt and the reaction mixture also contains at least one derivative of a metal of Group 3a or 4a of the Periodic Classification of Elements or of the lanthanide or actinide Groups selected from thallium, lead, cerium and uranium.
 6. A process according to claim 1 wherein the oxidation is carried out in the presence of an inert solvent.
 7. A process according to claim 6 wherein the inert solvent is at least one aliphatic hydrocarbon containing at least 4 carbon atoms, cycloaliphatic hydrocarbon or aromatic or alkyl aromatic hydrocarbons, alkyl-, cycloalkyl-, or aryl halide or an aliphatic carboxylic acid or ester thereof, a nitrile, a tertiary alcohol or a ketone.
 8. A process according to claim 7, wherein the solvent is acetic acid, cyclohexane, benzene, ethyl acetate, acetonitrile, tert. butanol, tert. amyl alcohol, acetone or methyl isopropyl ketone.
 9. A process according to claim 7, wherein the solvent is a mixture of a tertiary alcohol with an aliphatic carboxylic acid, hydrocarbon, akyl-, cycloalkyl- or aryl halide or nitrile.
 10. A process according to claim 9, wherein the solvent is a mixture of 10 to 90% by weight of an aliphatic carboxylic acid and 90 to 10% by weight of a tertiary alcohol. 